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      Human African Trypanosomiasis (sleeping sickness): Current knowledge and future challenges

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          Abstract

          According to both definitions of US Centers for Disease Control and Prevention and World Health Organization, Neglected Tropical Diseases (NTDs) are a group of preventable and treatable parasitic, viral, and bacterial diseases that affect more than one billion people globally. They generally afflict the more indigent patients of the world and historically have not received as much attention as other diseases. NTDs tend to thrive in low-income regions, where water quality, sanitation and access to health care are substandard. They are common in several countries of Africa, Asia, and Latin America. In this literature review, we want to focus on Human African Trypanosomiasis (HAT), also known as “sleeping sickness”, one of the most common neglected diseases in Africa. It is caused by infection with the subspecies of the parasitic protozoan Trypanosoma brucei, and it is transmitted by the bite of the tsetse fly. It puts 70 million people at risk throughout sub-Saharan Africa and it is usually fatal if untreated or inadequately treated. This review covers several aspects of the disease. We focused our interests on most recent epidemiological data, novel diagnostic methods with their advantages and limitations, new improved treatment and orphan drugs and eradication programs, including vector control, according to a “One Health” approach, to achieve the new goals recently set by WHO.

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          Most cited references143

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          The genome of the African trypanosome Trypanosoma brucei.

          African trypanosomes cause human sleeping sickness and livestock trypanosomiasis in sub-Saharan Africa. We present the sequence and analysis of the 11 megabase-sized chromosomes of Trypanosoma brucei. The 26-megabase genome contains 9068 predicted genes, including approximately 900 pseudogenes and approximately 1700 T. brucei-specific genes. Large subtelomeric arrays contain an archive of 806 variant surface glycoprotein (VSG) genes used by the parasite to evade the mammalian immune system. Most VSG genes are pseudogenes, which may be used to generate expressed mosaic genes by ectopic recombination. Comparisons of the cytoskeleton and endocytic trafficking systems with those of humans and other eukaryotic organisms reveal major differences. A comparison of metabolic pathways encoded by the genomes of T. brucei, T. cruzi, and Leishmania major reveals the least overall metabolic capability in T. brucei and the greatest in L. major. Horizontal transfer of genes of bacterial origin has contributed to some of the metabolic differences in these parasites, and a number of novel potential drug targets have been identified.
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            Human African trypanosomiasis.

            Human African trypanosomiasis (sleeping sickness) is a parasitic infection that almost invariably progresses to death unless treated. Human African trypanosomiasis caused devastating epidemics during the 20th century. Thanks to sustained and coordinated efforts over the past 15 years, the number of reported cases has fallen to an historically low level. Fewer than 3000 cases were reported in 2015, and the disease is targeted for elimination by WHO. Despite these recent successes, the disease is still endemic in parts of sub-Saharan Africa, where it is a considerable burden on rural communities, most notably in central Africa. Since patients are also reported from non-endemic countries, human African trypanosomiasis should be considered in differential diagnosis for travellers, tourists, migrants, and expatriates who have visited or lived in endemic areas. In the absence of a vaccine, disease control relies on case detection and treatment, and vector control. Available drugs are suboptimal, but ongoing clinical trials provide hope for safer and simpler treatments.
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              Nifurtimox-eflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: a multicentre, randomised, phase III, non-inferiority trial.

              Human African trypanosomiasis (HAT; sleeping sickness) caused by Trypanosoma brucei gambiense is a fatal disease. Current treatment options for patients with second-stage disease are toxic, ineffective, or impractical. We assessed the efficacy and safety of nifurtimox-eflornithine combination therapy (NECT) for second-stage disease compared with the standard eflornithine regimen. A multicentre, randomised, open-label, active control, phase III, non-inferiority trial was done at four HAT treatment centres in the Republic of the Congo and the Democratic Republic of the Congo. Patients aged 15 years or older with confirmed second-stage T b gambiense infection were randomly assigned by computer-generated randomisation sequence to receive intravenous eflornithine (400 mg/kg per day, every 6 h; n=144) for 14 days or intravenous eflornithine (400 mg/kg per day, every 12 h) for 7 days with oral nifurtimox (15 mg/kg per day, every 8 h) for 10 days (NECT; n=143). The primary endpoint was cure (defined as absence of trypanosomes in body fluids and a leucocyte count
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                Author and article information

                Journal
                Frontiers in Tropical Diseases
                Front. Trop. Dis
                Frontiers Media SA
                2673-7515
                May 9 2023
                May 9 2023
                : 4
                Article
                10.3389/fitd.2023.1087003
                76c2456d-8a3e-4873-808b-9c72dcf7d3b7
                © 2023

                Free to read

                https://creativecommons.org/licenses/by/4.0/

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